The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion

Nat Commun. 2018 Jul 30;9(1):2980. doi: 10.1038/s41467-018-05367-2.

Abstract

Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promotes the generation of suppressive cortical actin bundles that inhibit motility dynamics, and is crucial for the ER-mediated suppression of invasion in vitro and in vivo. Interestingly, despite its benefits in suppressing tumor growth, anti-estrogenic endocrine therapy decreases EVL expression and increases local invasion in patients. Our results highlight the dichotomous effects of estrogen on tumor progression and suggest that, in contrast to its established role in promoting growth of ER+ tumors, estrogen has a significant role in suppressing invasion through actin cytoskeletal remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actins / chemistry*
  • Animals
  • Breast Neoplasms / pathology*
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation
  • Dogs
  • Estradiol / chemistry
  • Estrogen Receptor alpha / chemistry*
  • Estrogens / chemistry*
  • Female
  • Gene Expression Profiling
  • HEK293 Cells
  • Humans
  • Lymph Nodes / pathology
  • MCF-7 Cells
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred NOD
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis
  • Transcription, Genetic

Substances

  • Actins
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogens
  • Estradiol